Biomedical subjects

Pawel Skudlarski

Publications and source records attributed to Pawel Skudlarski.

At least 19 recordsLinked to original sources

PubMed2006

Brain connectivity related to working memory performance.

Several brain areas show signal decreases during many different cognitive tasks in functional imaging studies, including the posterior cingulate cortex (PCC) and a medial frontal region incorporating portions of the medial frontal gyrus and ventral anterior cingulate cortex (MFG/vACC). It has been suggested that these areas are components in a default mode network that is engaged during rest and disengaged during cognitive tasks. This study investigated the functional connectivity between the PCC and MFG/vACC during a working memory task and at rest by examining temporal correlations in magnetic resonance signal levels between the regions. The two regions were functionally connected in both conditions. In addition, performance on the working memory task was positively correlated with the strength of this functional connection not only during the working memory task, but also at rest. Thus, it appears these regions are components of a network that may facilitate or monitor cognitive performance, rather than becoming disengaged during cognitive tasks. In addition, these data raise the possibility that the individual differences in coupling strength between these two regions at rest predict differences in cognitive abilities important for this working memory task.

Adult↗

PubMed2006

Connectivity-behavior analysis reveals that functional connectivity between left BA39 and Broca's area varies with reading ability.

Correlations between temporal fluctuations in MRI signals may reveal functional connectivity between brain regions within individual subjects. Such correlations would be especially useful indices of functional connectivity if they covary with behavioral performance or other subject variables. This study investigated whether such a relationship could be demonstrated in the context of the reading circuit in the brain. The method proved sufficiently powerful to reveal significant correlations between the reading abilities of subjects and the strength of their functional connection between left Brodmann's area 39 and Broca's area during reading. This suggests that the disconnection of the angular gyrus previously reported for dyslexic readers is part of a larger continuum in which poor (but nonimpaired readers) also show reduced connectivity to the region. In addition, it illustrates the potential power of paradigms that examine correlations between behavior and functional brain connections.

Adult↗

PubMed2006

A developmental fMRI study of self-regulatory control.

We used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of self-regulatory control across development in healthy individuals performing the Stroop interference task. Proper performance of the task requires the engagement of self-regulatory control to inhibit an automatized response (reading) in favor of another, less automatic response (color naming). Functional MRI scans were acquired from a sample of 70 healthy individuals ranging in age from 7 to 57 years. We measured task-related regional signal changes across the entire cerebrum and conducted correlation analyses to assess the associations of signal activation with age and with behavioral performance. The magnitude of fMRI signal change increased with age in the right inferolateral prefrontal cortex (Brodmann area [BA] 44/45) and right lenticular nucleus. Greater activation of the right inferolateral prefrontal cortex also accompanied better performance. Activity in the right frontostriatal systems increased with age and with better response inhibition, consistent with the known functions of frontostriatal circuits in self-regulatory control. Age-related deactivations in the mesial prefrontal cortex (BA 10), subgenual anterior cingulate cortex (BA 24), and posterior cingulate cortex (BA 31) likely represented the greater engagement of adults in self-monitoring and free associative thought processes during the easier baseline task, consistent with the improved performance on this task in adults compared with children. Although we cannot exclude the possibility that age-related changes in reading ability or in the strategies used to optimize task performance were responsible for our findings, the correlations of brain activation with performance suggest that changes in frontostriatal activity with age underlie the improvement in self-regulatory control that characterizes normal human development.

Adolescent↗

PubMed2006

Cue-induced brain activity changes and relapse in cocaine-dependent patients.

This study used functional magnetic resonance imaging (fMRI) to examine the association between brain activation during exposure to cocaine-related cues and relapse to drug use in cocaine-dependent (CD) patients. We imaged 17 CD subjects during a 2-week in-patient stay. The subjects then entered a 10-week outpatient placebo-controlled, double-blind randomized clinical trial where urine toxicologies were assessed three times weekly to calculate the treatment effectiveness score (TES). Worse TES correlated with BOLD activation in the left precentral, superior temporal, and posterior cingulate cortices (PCC), and right middle temporal and lingual cortices (R>0.65; P<0.005). The left PCC activation also distinguished eight nonrelapsers (TES above mean and completed treatment) from nine relapsers. Cocaine-free urines were significantly greater in the nonrelapsers (92%) than in the relapsers (66%), who also remained in treatment for an average of only 3.2 weeks. Self-reports of craving during fMRI did not differ between nonrelapsers and relapsers and did not correlate with TES. Relapse to cocaine abuse was associated with increased activation in the sensory association cortex, the motor cortex, and PCC while viewing images of cocaine-related cues. These results suggest that relapse to cocaine abuse is associated with increased brain activation to cocaine cues in sensory, motor, and cognitive-emotional processing areas. This physiological activation was a better predictor of relapse than subjective reports of craving, and may be a useful target for treatment development.

Adult↗

PubMed2005

Neural activity associated with stress-induced cocaine craving: a functional magnetic resonance imaging study.

OBJECTIVE: Stress is known to increase cocaine craving and relapse risk in cocaine dependence. Identifying neural activity associated with stress and stress-induced cocaine craving is important in understanding the neurobiology of cocaine craving and relapse. METHOD: Blood oxygenation level dependent (BOLD) signal changes were assessed in a functional magnetic resonance imaging (fMRI) session with healthy controls and treatment-engaged, abstinent, cocaine-dependent individuals (patients) as they participated in brief guided imagery and recall of three personal stress and three personal neutral situations. RESULTS: During stress, patients showed significantly less BOLD activation than controls in specific frontal and para-limbic regions, such as the anterior cingulate (AC) region, left hippocampal/parahippocampal region, right fusiform gyrus, and the right postcentral gyrus. On the other hand, patients had increased activity in the caudate and dorsal striatum region during stress, activation that was significantly associated with stress-induced cocaine craving ratings. CONCLUSIONS: Patients failed to activate AC and related circuits during stress, regions associated with control, and regulation of emotion and distress states. Instead, they exhibited greater craving-related activation in the dorsal striatum, a region related to reward pathways and part of the obsessive-compulsive circuitry. Such functional alterations in stress processing may underlie the stress-related vulnerability to cocaine relapse often observed in cocaine-dependent individuals in early recovery.

Adult↗

PubMed2005

DCDC2 is associated with reading disability and modulates neuronal development in the brain.

DYX2 on 6p22 is the most replicated reading disability (RD) locus. By saturating a previously identified peak of association with single nucleotide polymorphism markers, we identified a large polymorphic deletion that encodes tandem repeats of putative brain-related transcription factor binding sites in intron 2 of DCDC2. Alleles of this compound repeat are in significant disequilibrium with multiple reading traits. RT-PCR data show that DCDC2 localizes to the regions of the brain where fluent reading occurs, and RNA interference studies show that down-regulation alters neuronal migration. The statistical and functional studies are complementary and are consistent with the latest clinical imaging data for RD. Thus, we propose that DCDC2 is a candidate gene for RD.

Adult↗

PubMed2005

Preliminary evidence for medication effects on functional abnormalities in the amygdala and anterior cingulate in bipolar disorder.

RATIONALE: Abnormal amygdala and frontocortical responses to emotional stimuli are implicated in bipolar disorder (BD) and have been proposed as potential treatment targets. OBJECTIVES: The aim of this study was to investigate amygdala and frontocortical responses to emotional face stimuli in BD and the influences of mood-stabilizing medications on these responses. METHODS: Functional magnetic resonance imaging was performed while 17 BD participants (5 unmedicated) and 17 healthy comparison (HC) participants viewed faces with happy, sad, fearful, or neutral expressions. RESULTS: The group by stimulus-condition interaction was significant (p<0.01) for amygdala activation, with the greatest effects in the happy face condition. Relative to HC, amygdala increases were greater in unmedicated BD, but lower in medicated BD. Rostral anterior cingulate (rAC) activation was decreased in unmedicated BD compared to HC; however, BD participants taking medication demonstrated rAC activation similar to HC participants. CONCLUSIONS: Although the sample sizes were small, these preliminary results suggest that BD is associated with increased amygdala and decreased rAC response to emotional faces. The findings also provide preliminary evidence that mood-stabilizing medications may reverse abnormalities in BD in the response of an amygdala-frontal neural system to emotional stimuli.

Adult↗

PubMed2005

fMRI activation of the fusiform gyrus and amygdala to cartoon characters but not to faces in a boy with autism.

Abnormal hypoactivation in the amygdala and fusiform gyrus, brain areas that participate in face processing and social cognition, has consistently been demonstrated in persons with autism. We investigated activity in these areas in a boy with autism, DD, who had a special interest in "Digimon" cartoon characters. DD individuates Digimon faster than familiar faces and objects, but he individuates familiar faces no faster than objects. In contrast, a typically developing boy with an interest in "Pokemon" cartoon characters is equally fast at individuating faces and Pokemon and faster at individuating faces and Pokemon than objects and Digimon. In addition, using functional magnetic resonance imaging (fMRI), we show that DD activates his amygdala and fusiform gyrus for perceptual discriminations involving Digimon but not for those involving familiar or unfamiliar faces. This pattern of activation is not seen in the typically developing control with an interest in Pokemon or in a second comparison case who has autism but no interest in Digimon. These results have important implications for our understanding of autism, cortical face specialization, and the possible role of the amygdala in the development of perceptual expertise.

Amygdala↗

PubMed2005

Individual differences in FFA activity suggest independent processing at different spatial scales.

The brain processes images at different spatial scales, but it is unclear how far into the visual stream different scales remain segregated. Using functional magnetic resonance imaging, we found evidence that BOLD activity in the fusiform face area (FFA) reflects computations based on separate spatial frequency inputs. When subjects perform different tasks (attend location vs. identity; attend whole vs. parts) or the same task with different stimuli (upright or inverted) with high- and low-pass images of cars and faces, individual differences in the FFA in one condition are correlated with those in the other condition. However, FFA activity in response to low-pass stimuli is independent of its response to high-pass stimuli. These results suggest that spatial scales are not integrated before the FFA and that processing in this area could support the flexible use of different sources of information present in broad-pass images.

Brain Mapping↗

PubMed2004

Functional MRI changes before and after onset of reported emotions.

The social nature of emotion is evident in the importance of facial and vocal displays in emotion-related behavior. This is the first brain-imaging study to use simulated face-to-face social interactions to evoke emotional responses and to compare valence-related activations before and after subjective onset of emotional response. Videotapes were prepared with actresses who described happy or unhappy experiences. Functional magnetic resonance imaging (fMRI) at 1.5 T was used to acquire BOLD images in 21 healthy young adults before, after, and during viewing of the happy and sad tapes. Subjects pushed buttons to indicate the onset of subjective emotional responses. Group data were analyzed by a bootstrap randomization method after anatomical normalization. Significant activation was detected in frontal and sensory regions prior to the reported onset of emotional response, and this activity showed a marked decrease after the report of conscious emotional experience. Significant differences between happy and sad conditions were evident in multiple brain regions both before and after the reported onset of emotional response, including the middle and superior temporal gyri, the middle frontal gyrus, the caudate, and the hippocampus. Socially relevant emotional stimulation is feasible and evokes robust responses. The neural correlates of the evoked emotion are multiple, widely distributed, and inclusive of areas important in many cognitive tasks. Positive and negative emotional responses include activation of common and distinctive brain regions.

Adult↗

PubMed2004

Changes in functional connectivity of human MT/V5 with visual motion input.

The neural basis of human mental function is characterized by interactions between brain regions. Temporal correlations in MR signals between areas may provide one method for investigating these interactions. This approach was used to examine functional connectivity in the motion processing system of the human brain. Correlations between MT/V5 and other brain regions were examined in a resting state (without visual stimulation) and in an active state produced by viewing moving concentric circles. A network of regions consistent with the known functional anatomy of visual processing was correlated with MT/V5 during rest. When subjects were viewing motion, a more limited network was correlated with MT/V5, suggesting MT/V5 was acting in concert with a smaller network specific to the task.

Brain Mapping↗

PubMed2004

Development of left occipitotemporal systems for skilled reading in children after a phonologically- based intervention.

BACKGROUND: A range of neurobiological investigations shows a failure of left hemisphere posterior brain systems to function properly during reading in children and adults with reading disabilities. Such evidence of a disruption in the normal reading pathways provides a neurobiological target for reading interventions. In this study, we hypothesized that the provision of an evidence-based, phonologically mediated reading intervention would improve reading fluency and the development of the fast-paced occipitotemporal systems serving skilled reading. METHODS: Functional magnetic resonance imaging was used to study the effects of a phonologically based reading intervention on brain organization and reading fluency in 77 children aged 6.1-9.4 years (49 with reading disability and 28 control subjects). Children comprised three experimental groups: experimental intervention (n = 37), community intervention (n = 12), and community control subjects (n = 28). RESULTS: Immediately after the year-long intervention, children taught with the experimental intervention had made significant gains in reading fluency and demonstrated increased activation in left hemisphere regions, including the inferior frontal gyrus and the middle temporal gyrus; 1 year after the experimental intervention had ended these children were activating bilateral inferior frontal gyri and left superior temporal and occipitotemporal regions. CONCLUSIONS: These data indicate that the nature of the remedial educational intervention is critical to successful outcomes in children with reading disabilities and that the use of an evidence-based phonologic reading intervention facilitates the development of those fast-paced neural systems that underlie skilled reading.

Child↗

PubMed2004

Nicotine effects on brain function and functional connectivity in schizophrenia.

BACKGROUND: Nicotine in tobacco smoke can improve functioning in multiple cognitive domains. High rates of smoking among schizophrenic patients may reflect an effort to remediate cognitive dysfunction. Our primary aim was to determine whether nicotine improves cognitive function by facilitating activation of brain regions mediating task performance or by facilitating functional connectivity. METHODS: Thirteen smokers with schizophrenia and 13 smokers with no mental illness were withdrawn from tobacco and underwent functional magnetic resonance imaging (fMRI) scanning twice, once after placement of a placebo patch and once after placement of a nicotine patch. During scanning, subjects performed an n-back task with two levels of working memory load and of selective attention load. RESULTS: During the most difficult (dichotic 2-back) task condition, nicotine improved performance of schizophrenic subjects and worsened performance of control subjects. Nicotine also enhanced activation of a network of regions, including anterior cingulate cortex and bilateral thalamus, and modulated thalamocortical functional connectivity to a greater degree in schizophrenic than in control subjects during dichotic 2-back task performance. CONCLUSIONS: In tasks that tax working memory and selective attention, nicotine may improve performance in schizophrenia patients by enhancing activation of and functional connectivity between brain regions that mediate task performance.

Adult↗

PubMed2004

Parametric design and correlational analyses help integrating fMRI and electrophysiological data during face processing.

Face perception is typically associated with activation in the inferior occipital, superior temporal (STG), and fusiform gyri (FG) and with an occipitotemporal electrophysiological component peaking around 170 ms on the scalp, the N170. However, the relationship between the N170 and the multiple face-sensitive activations observed in neuroimaging is unclear. It has been recently shown that the amplitude of the N170 component monotonically decreases as gaussian noise is added to a picture of a face [Jemel et al., 2003]. To help clarify the sources of the N170 without a priori assumptions regarding their number and locations, ERPs and fMRI were recorded in five subjects in the same experiment, in separate sessions. We used a parametric paradigm in which the amplitude of the N170 was modulated by varying the level of noise in a picture, and identified regions where the percent signal change in fMRI correlated with the ERP data. N170 signals were observed for pictures of both cars and faces but were stronger for faces. A monotonic decrease with added noise was observed for the N170 at right hemisphere sites but was less clear on the left and occipital central sites. Correlations between fMRI signal and N170 amplitudes for faces were highly significant (P < 0.001) in bilateral fusiform gyrus and superior temporal gyrus. For cars, the strongest correlations were observed in the parahippocampal region and in the STG (P < 0.005). Besides contributing to clarify the spatiotemporal course of face processing, this study illustrates how ERP information may be used synergistically in fMRI analyses. Parametric designs may be developed further to provide some timing information on fMRI activity and help identify the generators of ERP signals.

Adult↗

PubMed2004

Neuronal representation of occluded objects in the human brain.

Occluding surfaces frequently obstruct the object of interest yet are easily dealt with by the visual system. Here, we test whether neural areas known to participate in motion perception and eye movements are regions that also process occluded motion. Functional magnetic resonance imaging (fMRI) was used to assess brain activation while subjects watched a moving ball become occluded. Areas activated during occluded motion included the intraparietal sulcus (IPS) as well as middle temporal (MT) regions analogous to monkey MT/MST. A second experiment showed that these results were not due to motor activity. These findings suggest that human cortical regions involved in perceiving occluded motion are similar to regions that process real motion and regions responsible for eye movements. The intraparietal sulcus may be involved in predicting the location of an unseen target for future hand or eye movements.

Adolescent↗

PubMed2004

Neural circuits underlying emotional distress in humans.

Difficulties in the experiences and regulation of emotional stress have been associated with the development of psychiatric and substance use disorders. This study examined neural circuits underlying emotional distress in healthy volunteers using functional magnetic resonance imaging (fMRI) techniques. Recall of personal nontraumatic, highly stressful life events with script-driven guided imagery was used to induce moderate levels of emotional distress in eight healthy volunteers. Subjects participated in six guided imagery trials (3 separate stress and 3 separate neutral-relaxing scripts each) interspersed by rest periods in a 1.5T scanner. Results indicated significant activation in the medial prefrontal, anterior cingulate, caudate, putamen, thalamus, hippocampus, parahippocampal gyrus, and posterior cingulate regions during emotional distress relative to brain activation during neutral-relaxing imagery. These findings suggest that specific striatal-limbic-prefrontal cortical circuits are involved in the experience and regulation of emotional stress in humans. The study also provides a feasible method to study brain correlates of emotional stress processing in healthy individuals and clinical samples.

Adult↗

PubMed2003

Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation.

BACKGROUND: Disturbed interpersonal relations and emotional dysregulation are fundamental aspects of borderline personality disorder (BPD). The amygdala plays important roles in modulating vigilance and generating negative emotional states and is often abnormally reactive in disorders of mood and emotion. The aim of this study was to assess amygdala reactivity in BPD patients relative to normal control subjects. We hypothesized that amygdala hyperreactivity contributes to hypervigilance, emotional dysregulation, and disturbed interpersonal relations in BPD. METHODS: Using functional magnetic resonance imaging, we examined neural responses to 20-sec blocks of neutral, happy, sad, and fearful facial expression (or a fixation point) in 15 BPD and 15 normal control subjects. The DSM IV-diagnosed BPD patients and the normal control subjects were assessed by a clinical research team in a medical school psychiatry department. RESULTS: Borderline patients showed significantly greater left amygdala activation to the facial expressions of emotion (vs. a fixation point) compared with normal control subjects. Post-scan debriefing revealed that some borderline patients had difficulty disambiguating neutral faces or found them threatening. CONCLUSIONS: Pictures of human emotional expressions elicit robust differences in amygdala activation levels in borderline patients, compared with normal control subjects, and can be used as probes to study the neuropathophysiologic basis of borderline personality disorder.

Adult↗

PubMed2003

Preliminary evidence of hippocampal dysfunction in adolescent MDMA ("ecstasy") users: possible relationship to neurotoxic effects.

RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) is a potent and selective serotonin neurotoxin whose use is growing among adolescents. Although cognitive deficits among adult MDMA users are well documented, little is known of the cognitive and brain functional sequelae of MDMA use during adolescence. OBJECTIVE: We tested for evidence of cognitive deficits and changes in brain function in a pilot sample of adolescent MDMA users, who were compared with adolescent non-users of MDMA. METHODS: Selective and divided attention and verbal working memory were examined in six adolescent MDMA users and six non-users of MDMA who were similar in age, gender, IQ, and other substance use. Brain function was assessed during performance of the working memory task using functional magnetic resonance imaging (fMRI). RESULTS: MDMA users had significantly prolonged reaction times during tests of selective and divided attention, and failed to deactivate the left hippocampus normally during high verbal working memory load. CONCLUSIONS: MDMA use in adolescence may be associated with cognitive impairments and dysfunction of inhibitory circuits within the hippocampus. Further work is urgently needed to delineate the developmental impact and long-term functional and clinical significance of MDMA use during adolescence.

Adolescent↗